Loss of doc2-dependent spontaneous neurotransmission augments glutamatergic synaptic strength

Denise M.O. Ramirez, Devon C. Crawford, Natali L. Chanaday, Brent Trauterman, Lisa M Monteggia, Ege T Kavalali

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Action potential-evoked vesicle fusion comprises the majority of neurotransmission within chemical synapses, but action potential-independent spontaneous neurotransmission also contributes to the collection of signals sent to the postsynaptic cell. Previous work has implicated spontaneous neurotransmission in homeostatic synaptic scaling, but few studies have selectively manipulated spontaneous neurotransmission without substantial changes in evoked neurotransmission to study this function in detail. Here we used a quadruple knockdown strategy to reduce levels of proteins within the soluble calcium-binding double C2 domain (Doc2)-like protein family to selectively reduce spontaneous neurotransmission in cultured mouse and rat neurons. Activity-evoked responses appear normal while both excitatory and inhibitory spontaneous events exhibit reduced frequency. Excitatory miniature postsynaptic currents (mEPSCs), but not miniature inhibitory postsynaptic currents (mIPSCs), increase in amplitude after quadruple knockdown. This increase in synaptic efficacy correlates with reduced phosphorylation levels of eukaryotic elongation factor 2 and also requires the presence of elongation factor 2 kinase. Together, these data suggest that spontaneous neurotransmission independently contributes to the regulation of synaptic efficacy, and action potential-evoked and spontaneous neurotransmission can be segregated at least partially on a molecular level.

Original languageEnglish (US)
Pages (from-to)6224-6230
Number of pages7
JournalJournal of Neuroscience
Volume37
Issue number26
DOIs
StatePublished - 2017

Keywords

  • Doc2
  • Spontaneous neurotransmitter release
  • Synaptic scaling

ASJC Scopus subject areas

  • Neuroscience(all)

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